A mechanistic review on immunomodulatory effects of selective type two cannabinoid receptor β‐caryophyllene

Abstract

β-Caryophyllene (BCP) is a plant-derived compound and occurs naturally in various foods and spices, including cinnamon, citrus, fruits, clove, curry, and pepper. BCP showed different pharmacological effects, such as antioxidant and antimicrobial properties. This article tried to gather updated knowledge of the anti-inflammatory, antioxidant, and immunomodulatory effects of BCP and searched using various databases and appropriate keywords until April 2022. Several studies showed that the anti-inflammatory effects of BCP are mainly provided through cannabinoid receptor 2 (CB 2 ) receptor activation and the peroxisome proliferator-activated receptor (PPAR) γ pathway. It has also been demonstrated that BCP suppresses both protein and mRNA expression levels of interleukin (IL)-6 and reduces relevant proinflammatory cytokines but increases the anti-inflammatory cytokine IL-13. Previous results indicated that the antioxidant effects of β-caryophyllene were suggested through different pathways, including activation of nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1)/antioxidant axis and inhibition of the HMG-CoA reductase activity, and oxidative stress biomarkers levels. Furthermore, various results showed immunomodulatory effects of BCP through inhibiting microglial cells, CD 4+ and CD 8+ T lymphocytes, modulated Th 1 /T reg immune balance through the activation of the CB 2 receptor, and reducing mitogenactivated protein kinases (p38MAPK) and NF-kB activation and increased ionized calcium-binding adaptor molecule-1 (Iba-1) and IL-1β.

Correlation between the Skin Permeation Profile of the Synthetic Sesquiterpene Compounds, Beta-Caryophyllene and Caryophyllene Oxide, and the Antiedematogenic Activity by Topical Application of Nanoemulgels

“…The composition of COP determined in this study was in accordance with previous studies, which reported contents of CAR in the range of 5.08 to 62.70% and OX from 0.22 to 58.40% [ 9 , 10 , 16 , 30 ]. Together, these data support the definition of CAR and OX as major sesquiterpenes of C. multijuga oleoresin.…”

“…Recent studies have described the mechanisms of CAR action in inflammatory processes, in particular, the action of CAR on the enzymes, cyclooxygenase-2 (COX-2), and lipoxygenase-5 (LOX-5), thereby reducing the release of inflammatory mediators, mitigating the symptoms of pain and edema, and highlighting its healing property [ 2 , 3 , 4 , 5 , 6 ]. The broad pharmacological potential of CAR is highlighted in the reviews by Sharma et al (2016), Francomano et al (2019), and Rahimi and Askari [ 7 , 8 , 9 ]. Additionally, studies have highlighted CAR as a promising compound for pain management owing to its action in the endocannabinoid system via selective interaction with cannabinoid 2 (CB2) receptors, thus providing analgesic action [ 2 , 10 , 11 ].…”

Pinus halepensis Essential Oil Ameliorates Aβ1-42-Induced Brain Injury by Diminishing Anxiety, Oxidative Stress, and Neuroinflammation in Rats

“…Myrcene appears to manifest its antioxidant properties by upregulating Nrf2 transcription factor gene expression, as well as the expression of its target genes CAT, SOD1, GPX1, GSTP1, NQO1, GSR, and HMOX1 [ 120 ]. Antioxidant and neuroprotective effects of β -caryophyllene seem to be linked to G-protein-coupled type 2 cannabinoid receptor (CB2R)-dependent Nrf2/heme oxygenase-1 (HO-1) antioxidant axis activation and inhibition of the HMG-CoA reductase activity [ 121 , 122 , 123 ].…”

Promising influences of gingerols against metabolic syndrome: A mechanistic review

“…Diabetes mellitus (DM) is a chronic metabolic disease caused by hyperglycemia, inadequate insulin production, or inadequate insulin sensitivity. [4][5][6] Diabetic types include type 1, 2, and gestational diabetes. [34][35][36] In fact, MS is strongly linked to the occurrence of type 2 diabetes 37 and is characterized by insulin resistance.…”

“…Therefore, finding efficient methods to identify, manage, and treat MS-related comorbidities has drawn increasing interest. [4][5][6] However, chemical or synthetic drugs have limitations and unpleasant adverse effects. In contrast, the demand for medicinal plants with minimal adverse effects, reputedly, to treat MS has increased.…”